GUT MICROBIOTA METABOLITES AND HOLTER ECG MONITORING IN CORONARY ARTERY DISEASE PATIENTS WITH ATRIAL FIBRILLATION

Gut microbiota metabolites play a clue role in human metabolism. The aim: To analyze and find the connections between Holter ECG monitoring indexes and gut microbiota metabolites in patients with coronary artery disease and atrial fibrillation. Materials and methods: 300 patients were divided into 3 groups: first (CAD) – 149 patients with CAD but without arrhythmias, second (CAD+AF) – 124 patients with CAD and AF paroxysm, and the control group – 27 patients without CAD and arrhythmias. Holter ECG monitoring was done for the patients with AF paroxysm within 24 hours after sinus rhythm restoration, and for the patients without AF on the first day of observation. A channel Holter ECG monitor (Cardiosens_K, Kharkiv, 2014) was used. We assessed Holter monitoring in V1, aVF, and V5 leads during 24 hours. The levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO) in plasma, and fecal short-chain fatty acids (SCFA) were determined by gas chromatography with mass electron detection. Results: Isocaproic and isobutyric fecal acids occurred in the I and II groups in comparison with the CG. In the II group patients an increase of TMA (16.13%), and TMAO (57.54%) levels and a decrease in their ratio (26.16%) was found in comparison with the I group, P<0.05. In the II group patients an increase in valeric (1128.43%) and a decrease in butyric (78.75%), isovaleric (43.71%), caprylic (99.21%) acids, middle chain fatty acids (95.54%), and the total amount of fecal SCFA (17.09%) was found in comparison with the I group, P<0.05. In the II group patients, an increase in supraventricular and ventricular extrasystoles was checked in comparison with the I group patients, P<0.05. The significant middle force correlations between rhythm abnormalities and gut microbiota metabolites were found: supraventricular extrasystoles per hour and TMA (r=0.311), TMAO (r=0.364), the total amount of fecal SCFA (r=-0.339), and butyric acid (r=-0.321); ventricular extrasystoles per hour and trimethylamine (r=0.320), trimethylamine-N-oxide (r=0.373), the total amount of fecal SCFA (r=-0.309), and isocaproic acid (r=0.399); AF episodes occurrence correlated with TMAO (r=0.355), butyric acid (r=-0.312), isobutyric acid (r=-0.319), middle chain fatty acids (r=-0.334), P<0.05. The significant middle force correlations between ST-segment changes and TMAO (r=0.390), the total amount of fecal SCFA (r=-0.398), unsaturated fatty acids (r=-0.307), butyric acid (r=-0.336), valeric acid (r=0.317) were checked, P<0.05. The maximum ST-episode duration was significantly correlated with TMAO (r=0.326), the total amount of fecal SCFA (r=-0.391), valeric acid (r=-0.322), P<0.05. Conclusion: Gut microbiota metabolites (TMA, TMAO, fecal SCFA) are significantly correlated with rhythm abnormalities (supraventricular and ventricular) and ST-segment changes in CAD patients. TMA and TMAO were directly correlated with AF paroxysms, supraventricular, and ventricular rhythm abnormalities, which shows them as a new therapeutic target for patients with CAD and AF. Vice versa the total amount of fecal SCFA, butyric, and valeric acids had inversing associations with rhythm abnormalities, which present them as a promising therapeutic molecule for CAD and AF management. However, the pathogenetic mechanisms of influence gut microbiota metabolites on rhythm abnormalities and myocardial ischemia need further investigation.